Bottom Line:
The defects of abl mutants are strongly enhanced by heterozygosity for shotgun, which encodes DE-cadherin.Finally, loss of Abl reduces Arm and alpha-catenin accumulation in adherens junctions, while having little or no effect on other components of the cytoskeleton or cell polarity machinery.We discuss possible models for Abl function during epithelial morphogenesis in light of these data.

Affiliation: Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3280, USA.

ABSTRACTActivation of the nonreceptor tyrosine kinase Abelson (Abl) contributes to the development of leukemia, but the complex roles of Abl in normal development are not fully understood. Drosophila Abl links neural axon guidance receptors to the cytoskeleton. Here we report a novel role for Drosophila Abl in epithelial cells, where it is critical for morphogenesis. Embryos completely lacking both maternal and zygotic Abl die with defects in several morphogenetic processes requiring cell shape changes and cell migration. We describe the cellular defects that underlie these problems, focusing on dorsal closure as an example. Further, we show that the Abl target Enabled (Ena), a modulator of actin dynamics, is involved with Abl in morphogenesis. We find that Ena localizes to adherens junctions of most epithelial cells, and that it genetically interacts with the adherens junction protein Armadillo (Arm) during morphogenesis. The defects of abl mutants are strongly enhanced by heterozygosity for shotgun, which encodes DE-cadherin. Finally, loss of Abl reduces Arm and alpha-catenin accumulation in adherens junctions, while having little or no effect on other components of the cytoskeleton or cell polarity machinery. We discuss possible models for Abl function during epithelial morphogenesis in light of these data.

Mentions:
We saw strong genetic interactions of abl with the cadherin shg, but not with the integrin scb. We crossed females with abl mutant germlines to males heterozygous for shg or scb. All progeny lack maternal Abl and are zygotically abl heterozygous, receiving a wild-type copy paternally. Zygotic wild-type Abl normally rescues all of these embryos to viability (Table I). However, shg2 heterozygosity led to lethality of abl/+ embryos (Table I). Only 40% of the progeny hatch, and the dead embryos have dorsal closure and germband retraction defects similar to ablMZ mutants. Many also have severe defects in head involution (Fig. 8 B, arrow). Similar, though somewhat less penetrant, results were seen with the shg allele, shgR69 (Table I). In contrast, we saw no effects on the survival of abl/+ embryos of removing one copy of scb (Table I). To increase the sensitivity of this genetic interaction assay, we crossed females with abl mutant germ lines to abl/+; shg/+ or abl/+; scb/+ males. Half of the progeny lack both maternal and zygotic Abl, and half of those are also heterozygous for either shg or scb. Heterozygosity for shg2 substantially enhanced the ablMZ phenotype (Fig. 8 D; Table II). Approximately half of the dead embryos (presumably those that were abl/abl; shg2/+) had a prominent dorsal anterior hole not seen in ablMZ mutants (Fig. 8 D); these embryos also had the typical spectrum of dorsal closure and germband retraction defects. We saw similar phenotypic enhancement in ablMZ embryos heterozygous for the shg allele, shgR69. (Fig. 8 E; Table II). In contrast, this sensitized assay did not uncover a significant genetic interaction between abl and scb (Table II).

Mentions:
We saw strong genetic interactions of abl with the cadherin shg, but not with the integrin scb. We crossed females with abl mutant germlines to males heterozygous for shg or scb. All progeny lack maternal Abl and are zygotically abl heterozygous, receiving a wild-type copy paternally. Zygotic wild-type Abl normally rescues all of these embryos to viability (Table I). However, shg2 heterozygosity led to lethality of abl/+ embryos (Table I). Only 40% of the progeny hatch, and the dead embryos have dorsal closure and germband retraction defects similar to ablMZ mutants. Many also have severe defects in head involution (Fig. 8 B, arrow). Similar, though somewhat less penetrant, results were seen with the shg allele, shgR69 (Table I). In contrast, we saw no effects on the survival of abl/+ embryos of removing one copy of scb (Table I). To increase the sensitivity of this genetic interaction assay, we crossed females with abl mutant germ lines to abl/+; shg/+ or abl/+; scb/+ males. Half of the progeny lack both maternal and zygotic Abl, and half of those are also heterozygous for either shg or scb. Heterozygosity for shg2 substantially enhanced the ablMZ phenotype (Fig. 8 D; Table II). Approximately half of the dead embryos (presumably those that were abl/abl; shg2/+) had a prominent dorsal anterior hole not seen in ablMZ mutants (Fig. 8 D); these embryos also had the typical spectrum of dorsal closure and germband retraction defects. We saw similar phenotypic enhancement in ablMZ embryos heterozygous for the shg allele, shgR69. (Fig. 8 E; Table II). In contrast, this sensitized assay did not uncover a significant genetic interaction between abl and scb (Table II).

Bottom Line:
The defects of abl mutants are strongly enhanced by heterozygosity for shotgun, which encodes DE-cadherin.Finally, loss of Abl reduces Arm and alpha-catenin accumulation in adherens junctions, while having little or no effect on other components of the cytoskeleton or cell polarity machinery.We discuss possible models for Abl function during epithelial morphogenesis in light of these data.

Affiliation:
Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3280, USA.

ABSTRACTActivation of the nonreceptor tyrosine kinase Abelson (Abl) contributes to the development of leukemia, but the complex roles of Abl in normal development are not fully understood. Drosophila Abl links neural axon guidance receptors to the cytoskeleton. Here we report a novel role for Drosophila Abl in epithelial cells, where it is critical for morphogenesis. Embryos completely lacking both maternal and zygotic Abl die with defects in several morphogenetic processes requiring cell shape changes and cell migration. We describe the cellular defects that underlie these problems, focusing on dorsal closure as an example. Further, we show that the Abl target Enabled (Ena), a modulator of actin dynamics, is involved with Abl in morphogenesis. We find that Ena localizes to adherens junctions of most epithelial cells, and that it genetically interacts with the adherens junction protein Armadillo (Arm) during morphogenesis. The defects of abl mutants are strongly enhanced by heterozygosity for shotgun, which encodes DE-cadherin. Finally, loss of Abl reduces Arm and alpha-catenin accumulation in adherens junctions, while having little or no effect on other components of the cytoskeleton or cell polarity machinery. We discuss possible models for Abl function during epithelial morphogenesis in light of these data.